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Nat Cell Biol. 2017 Sep;19(9):1017-1026. doi: 10.1038/ncb3575. Epub 2017 Aug 14.

Lactate dehydrogenase activity drives hair follicle stem cell activation.

Author information

1
Department of Molecular Cell and Developmental Biology, UCLA, 90095, USA.
2
Eli and Edythe Broad Center for Regenerative Medicine, UCLA, 90095, USA.
3
Molecular Biology Institute, UCLA, 90095, USA.
4
Department of Biochemistry, University of Utah, 84322, USA.
5
Department of Molecular and Medical Pharmacology, UCLA, 90095, USA.
6
Stanford School of Medicine, Stanford University, 94305, USA.
7
UCLA Metabolomics Center, UCLA, 90095, USA.
8
School of Veterinary Medicine, Cornell University, 14853, USA.
9
Mork Family Department of Chemical Engineering, University of Southern California, 90089, USA.
10
Crump Institute for Molecular Imaging, UCLA, 90095, USA.
11
Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Cancer Center, Harvard Medical School, 02215, USA.
12
Broad Center for Regenerative Medicine, University of Southern California, 90089, USA.
13
Jonsson Comprehensive Cancer Center, UCLA, 90095, USA.
14
Department of Biological Chemistry, UCLA, 90095, USA.
15
Howard Hughes Medical Institute, 20815, USA.

Abstract

Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.

PMID:
28812580
PMCID:
PMC5657543
DOI:
10.1038/ncb3575
[Indexed for MEDLINE]
Free PMC Article

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